Hybrid fuzzy/crisp-logic control of manufacturing systems

In recent years, techniques such as dynamic programming, the maximum principle, linear programming, and genetic algorithms have been used to synthesise optimal control policies for manufacturing systems. However, such techniques are frequently rather opaque and often yield control policies that are implemented by open-loop rather than closed-loop control systems. In this paper, it is therefore shown that closed-loop systems incorporating hybrid fuzzy/crisp-logic controllers can be readily designed for manufacturing systems. This hybrid approach is illustrated by reference to the closed-loop control of a simple manufacturing system producing a single part type.published_or_final_versio

Effects of Hikers and Boats on Tule Elk Behavior in a National Park Wilderness Area

Human disturbance of wildlife may cause disruption of normal feeding, resting, reproduction, or care for juveniles. Such disturbance may be particularly undesirable in federally managed wilderness areas designed to minimize human influences on natural resources. We recorded tule elk (Cervus elephus nannodes) responses (standing, walking away, running) to off-trail hikers, off-shore boats, and other natural and anthropogenic factors in Point Reyes National Seashore in northern California during 2002 to 2008. Most disturbance behaviors were related to other elk exhibiting rutting behaviors, but off-trail hikers still explained a 100% increase and off-shore boats a 15% increase in baseline disturbance behaviors by elk. However, off-trail hikers and boats did not cause elk to enter or leave the study area during the sample periods. Elk were more prone to human disturbance when herd sizes wereand, to a lesser extent, offshore boats appear to disturb natural tule elk behavior, but the physiological or population-level effects of this disturbance are unknown. Our quantitative results may help park managers minimize or mitigate human–elk interactions in wilderness areas

Agrobacterium-mediated gene delivery and transient expression in the red macroalga Chondrus crispus

Molecular resources and transgenic studies in red algae are lagging behind those for green algae. The Agrobacterium-mediated gene-transfer method routinely used in plant transformation has not been fully utilised in the red algae, which, as an important source of phycocolloids, warrant more studies. In this regard, a stepwise methodology was developed for Agrobacterium-mediated transformation of the carrageenophyte Chondrus crispus using pCAMBIA 1301 and a construct featuring a codon-optimized beta-glucuronidase (GUS) reporter gene driven by the endogenous Chondrus actin promoter. The effects of several factors on transformation efficiency were investigated. An intimate association of Chondrus and bacterial cells was observed using scanning electron microscopy. GUS transient expression within Chondrus cortical and medullary cells with both expression cassettes testified to the amenability of Chondrus to Agrobacterium-mediated transformation. Darker staining, indicative of higher GUS activity, was observed with the Chondrus-specific construct, suggesting its superiority over the pCAMBIA 1301. Presence of acetosyringone, the wounding method and the type of co-cultivation medium significantly affected the transformation outcome and efficiency. The Agrobacterium-mediated transient expression presented here constitutes a first step towards tailoring a transformation strategy for Chondrus, which can serve to facilitate further transgenic studies in this important red alga

Gene Duplication and Gain in the Trematode Atriophallophorus winterbourni Contributes to Adaptation to Parasitism.

Gene duplications and novel genes have been shown to play a major role in helminth adaptation to a parasitic lifestyle because they provide the novelty necessary for adaptation to a changing environment, such as living in multiple hosts. Here we present the de novo sequenced and annotated genome of the parasitic trematode Atriophallophorus winterbourni and its comparative genomic analysis to other major parasitic trematodes. First, we reconstructed the species phylogeny, and dated the split of A. winterbourni from the Opisthorchiata suborder to approximately 237.4 Ma (±120.4 Myr). We then addressed the question of which expanded gene families and gained genes are potentially involved in adaptation to parasitism. To do this, we used hierarchical orthologous groups to reconstruct three ancestral genomes on the phylogeny leading to A. winterbourni and performed a GO (Gene Ontology) enrichment analysis of the gene composition of each ancestral genome, allowing us to characterize the subsequent genomic changes. Out of the 11,499 genes in the A. winterbourni genome, as much as 24% have arisen through duplication events since the speciation of A. winterbourni from the Opisthorchiata, and as much as 31.9% appear to be novel, that is, newly acquired. We found 13 gene families in A. winterbourni to have had more than ten genes arising through these recent duplications; all of which have functions potentially relating to host behavioral manipulation, host tissue penetration, and hiding from host immunity through antigen presentation. We identified several families with genes evolving under positive selection. Our results provide a valuable resource for future studies on the genomic basis of adaptation to parasitism and point to specific candidate genes putatively involved in antagonistic host-parasite adaptation

Personalized Cytokine-Directed Therapy With Tocilizumab for Refractory Immune Checkpoint Inhibitor-Related Cholangiohepatitis.

For patients with corticosteroid (CS)-refractory immune checkpoint inhibitor-related cholangiohepatitis (irCH), no consensus exists regarding treatment, and outcomes remain poor. We evaluated the possibility of personalized treatment according to the patient's cytokine profile and the immunohistopathologic assessment of the predominant immune infiltrate type of liver tissue. NSCLCs with CS-refractory irCH were analyzed by immunohistochemistry of liver biopsy specimen, serum cytokine panel, and assessment of peripheral blood mononuclear cell immune cell monitoring by mass cytometry. A total of three consecutive patients with irCH were identified. We found a predominant T-cell infiltrate and an interferon-gamma or T helper 1 proinflammatory cytokine profile. Here, we report for the first time that a T-cell-targeted therapy with the interleukin (IL)-6 receptor-neutralizing antibody tocilizumab, which inhibits signaling downstream of interferon-gamma and several other Janus kinase-dependent cytokines, is an effective single cytokine-directed therapy for CS-refractory irCH. Three patients with severe, CS-refractory irCH who were treated with tocilizumab were found to have persistent clinical and biological remission. Dysregulation of the IL-6/T-cell axis may contribute to the pathogenesis of CS-refractory irCH. Our observations suggest that IL-6 blockade seems to have promise in the treatment of CS-refractory irCH. The results from our three patients need to be confirmed in a larger patient population

Looking in the mirror for the first time after facial burns: a retrospective mixed methods study

Appearance-related concerns are common following burns. However, there is minimal research that has specifically investigated patients' reactions when they looked in the mirror for the first time following facial burns. The current study aimed to investigate patients' reactions and factors associated with distress. Burns patients (n=35) who had sustained facial injuries completed a questionnaire which examined their reactions when looking in the mirror for the first time. Data were collected between April and July 2013. Participants had sustained their burns 12 months prior to participating, on average (ranging from one to 24 months). Forty-seven percent (n=16) of patients were worried about looking for the first time, 55% (n=19) were concerned about what they would see, and 42% (n=14) held negative mental images about what their faces looked like before they looked. Twenty-seven percent (n=9) of patients initially avoided looking, 38% (n=13) tried to 'read' others' reactions to them to try to gauge what they looked like, and 73% (n=25) believed that it was important for them to look. Mean ratings suggested that patients found the experience moderately distressing. Patients most often found the experience less distressing compared to their expectations. Distress was related to feeling less prepared, more worried and increased negative mental images prior to looking. In conclusion, patients' reactions to looking in the mirror for the first time vary. Adequately preparing patients and investigating their expectations beforehand is crucial. The findings have a number of important implications for practice

OMA orthology in 2021: website overhaul, conserved isoforms, ancestral gene order and more

OMA is an established resource to elucidate evolutionary relationships among genes from currently 2326 genomes covering all domains of life. OMA provides pairwise and groupwise orthologs, functional annotations, local and global gene order conservation (synteny) information, among many other functions. This update paper describes the reorganisation of the database into gene-, group- and genome-centric pages. Other new and improved features are detailed, such as reporting of the evolutionarily best conserved isoforms of alternatively spliced genes, the inferred local order of ancestral genes, phylogenetic profiling, better cross-references, fast genome mapping, semantic data sharing via RDF, as well as a special coronavirus OMA with 119 viruses from the Nidovirales order, including SARS-CoV-2, the agent of the COVID-19 pandemic. We conclude with improvements to the documentation of the resource through primers, tutorials and short videos. OMA is accessible at https://omabrowser.org

Dengue Virus Infection-Enhancing Activity in Serum Samples with Neutralizing Activity as Determined by Using FcγR-Expressing Cells

Dengue has become a major international public health concern in recent decades. There are four dengue virus serotypes. Recovery from infection with one serotype confers life-long protection to the homologous serotype but only partial protection to subsequent infection with other serotypes. Secondary infection with a serotype different from that in primary infection increases the risk of development of severe complications. Antibodies may play two competing roles during infection: virus neutralization that leads to protection and recovery, or infection-enhancement that may cause severe complications. Progress in vaccine development has been hampered by limited understanding on protective immunity against dengue virus infection. We report the neutralization activity and infection-enhancement activity in individuals with dengue in Malaysia. We show that infection-enhancement activity is present when neutralizing activity is absent or low, and cross-reactive neutralizing activity may be hampered by infection-enhancing activity. Conventional assays for titration of neutralizing antibody do not consider infection-enhancement activity. We used an alternative assay that determines the sum of neutralizing and infection-enhancement activity in sera from dengue patients. In addition to providing insights into antibody responses during infection, the alternative assay provides a new platform for the study of immune responses to vaccine